Project Summary Improvements in the surgical and medical care of children with congenital heart disease (CHD) have increased survival. Among survivors, however, there is a high prevalence and significant long term impact of cognitive and behavioral problems and medical complications including heart failure and problems with growth. We hypothesize that in some cases of CHD, there are genes that have pleiotropic effects on development and function of other systems including the brain. The goal of this study is to determine the genetic contributions to clinical outcomes in individuals with CHD and to begin to use this information in clinical care and to design better clinical trials of treatments for CHD. Through these studies, we will determine major genetic contributors to CHD outcomes, expand the scientific evidence through additional case finding outside of PCGC to increase the number of confirmed CHD genes and clinically characterize these genetic conditions to improve the ability to anticipate and prevent medical problems in those CHD patients. By identifying individuals with pathogenic variants from previous clinical trials, we will determine whether integration of genomic data would improve power and precision for CHD treatment trials by eliminating groups of patients unlikely to respond. All of these efforts are focused on translating the findings from PCGC into clinical care.